Jesse Gelsinger (June 18, 1981 – September 17, 1999) was the first person publicly identified as having died in a clinical trial for gene therapy. Gelsinger suffered from ornithine transcarbamylase deficiency, an X-linked genetic disease of the liver, the symptoms of which include an inability to metabolize ammonia – a byproduct of protein breakdown. The disease is usually fatal at birth, but Gelsinger had a milder form of the disease, in which the ornithine transcarbamylase gene is mutated in only part of the patient's cells, a condition known as somatic mosaicism. As his deficiency was partial, Gelsinger managed to survive on a restricted diet and special medications.
Gelsinger joined a clinical trial run by the University of Pennsylvania that aimed at developing a treatment for infants born with the severe form of the disease. On September 13, 1999, Gelsinger was injected with an adenoviral vector carrying a corrected gene to test the safety of the procedure. He died four days later at the age of 18, on September 17, apparently having suffered a massive immune response triggered by the use of the viral vector to transport the gene into his cells, leading to multiple organ failure and brain death.
A Food and Drug Administration (FDA) investigation concluded that the scientists involved in the trial, including the co-investigator James Wilson (Director of the Institute for Human Gene Therapy), broke several rules of conduct:
- Inclusion of Gelsinger as a substitute for another volunteer who dropped out, despite Gelsinger's having high ammonia levels that should have led to his exclusion from the trial.
- Failure by the university to report that two patients had experienced serious side effects from the gene therapy.
- Failure to disclose, in the informed-consent documentation, the deaths of monkeys given a similar treatment.
The University of Pennsylvania later issued a rebuttal, but the university and Children's National Medical Center each agreed to pay more than $500,000 to the government. Both Wilson and the University are reported to have had financial stakes in the research. The Gelsinger case was a severe setback for scientists working in the field.
- Stolberg, Sheryl Gay (November 28, 1999). "The Biotech Death of Jesse Gelsinger". The New York Times Magazine. Retrieved July 5, 2018.
- "Institute for Human Gene Therapy Responds to FDA – Almanac Between Issues". Upenn.edu. 2000-02-14. Retrieved 2010-11-16.
- Branca, MA (May 2005). "Gene therapy: cursed or inching towards credibility?". Nature Biotechnology. 23 (5): 519–21. doi:10.1038/nbt0505-519. PMID 15877060.
- Greenberg, Daniel S. "Science for Sale. The Perils, Rewards, and Delusions of Campus Capitalism". Chicago: U. Chicago Press, 2007, 324pp., pages 104–106.
- "Don't Compromise Ethics in Human Experiments, Bioethics Expert Says". Law.virginia.edu. 2008-04-18. Retrieved 2010-11-16.
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- Another Chance For Gene Therapy?: https://www.wired.com/1999/10/another-chance-for-gene-therapy/
- Paul Gelsinger, Jesse's father, tells of Jesse's death: http://www.guineapigzero.com/jesses-intent.html
- On gene therapy and informed consent (2008 debate): http://blog.bioethics.net/2008/01/on-gene-therapy-and-informed-consent/#comments
- BBC Horizon Trial and error – the rise and fall of genome therapy: http://www.bbc.co.uk/science/horizon/2003/trialerror.shtml
- FDA Notice Of Opportunity for Hearing to James Wilson: https://www.fda.gov/regulatoryinformation/foi/electronicreadingroom/ucm144564.htm